Bordetella pertussis (B. pertussis) is a gram-negative bacterium that infects the upper respiratory tract, causing uncontrollable, violent coughing. According to the World Health Organization, B. pertussis infection causes an estimated 300,000 deaths worldwide each year, primarily among young, unvaccinated infants. Infants with pertussis often require hospitalization in pediatric intensive care units, and their treatments frequently involve mechanical ventilation. Pertussis in adults generally leads to a chronic cough referred to as the “cough of 100 days.” The incidence of pertussis is increasing due to exposures of unvaccinated and under-vaccinated individuals including infants who are not yet fully vaccinated, individuals whose immunity has diminished over time, and asymptomatic carriers.
Recent news reports throughout the United States indicate that the pertussis vaccine introduced in the 1990s does not provide long-term protection. There is no approved treatment for pertussis. Antibiotic treatments do not have a major effect on the course of pertussis, because while the treatment can eliminate the B. pertussis bacteria from the respiratory tract, it does not neutralize the pertussis toxin protein. Accordingly, there remains a need for more effective therapies against pertussis.
Further, in the developing world, access to the existing pertussis vaccine, however flawed, is inconsistent and often difficult.
Naturally occurring antibodies are multimeric proteins that contain four polypeptide chains. Two of the polypeptide chains are called heavy chains (H chains), and two of the polypeptide chains are called light chains (L chains). The immunoglobulin heavy and light chains are connected by an interchain disulfide bond. The immunoglobulin heavy chains are connected by interchain disulfide bonds. A light chain consists of one variable region (VL) and one constant region (CL). The heavy chain consists of one variable region (VH) and at least three constant regions (CH1, CH2 and CH3). The variable regions determine the specificity of the antibody. Each variable region comprises three hypervariable regions also known as complementarity determining regions (CDRs) flanked by four relatively conserved framework regions (FRs). The three CDRs, referred to as CDR1, CDR2, and CDR3, contribute to the antibody binding specificity. Naturally occurring antibodies have been used as starting material for engineered antibodies, such as humanized antibodies.
Antibodies that bind the pertussis toxin protein have been developed, but the effectiveness of these antibodies in patients is either minimal or unclear. There remains a need for improved antibodies against the pertussis toxin protein with increased efficacy and reduced sides effects to be used as therapeutics.